Nova Scotia Home for Colored Children Restorative Inquiry: Council of Parties Second Public Report

The Nova Scotia Home for Colored Children Restorative Inquiry was established following a 17-year journey for justice by former residents of the Nova Scotia Home for Colored Children (NSHCC, or the Home). It was established under the authority of the Public Inquiries Act following a collaborative design process involving former residents, Government, and community members. This public inquiry was the first of its kind in Canada to take a restorative approach. The Inquiry was a part of the Government of Nova Scotia’s commitment to respond to the institutional abuse and other failures of care experienced by former residents of the Nova Scotia Home for Colored Children. In establishing the Restorative Inquiry, the Government of Nova Scotia recognized that the history, experience, and legacy of the Home reflects the systemic and institutionalized racism that has shaped Nova Scotia’s history and continues to impact the lives and experiences of African Nova Scotians to this day. This public report is issued by the Council of Parties of the Nova Scotia Home for Colored Children Restorative Inquiry (RI). It is one of many public reporting opportunities that will be part of the work of the RI during its mandate. The Council of Parties is the collaborative commission that leads the Restorative Inquiry, appointed as “commissioners” under the Public Inquiries Act. The council is mandated to include representation from the groups most affected by and involved in the work of the Restorative Inquiry, including former residents, the Home for Colored Children, the African Nova Scotian community, and government

Nova Scotia Home for Colored Children Restorative Inquiry: Council of Parties Third Public Report

The Nova Scotia Home for Colored Children Restorative Inquiry was established following a 17-year journey for justice by former residents of the Nova Scotia Home for Colored Children (NSHCC, or the Home). It was established under the authority of the Public Inquiries Act following a collaborative design process involving former residents, Government, and community members. This public inquiry was the first of its kind in Canada to take a restorative approach. The Inquiry was a part of the Government of Nova Scotia’s commitment to respond to the institutional abuse and other failures of care experienced by former residents of the Nova Scotia Home for Colored Children. In establishing the Restorative Inquiry, the Government of Nova Scotia recognized that the history, experience, and legacy of the Home reflects the systemic and institutionalized racism that has shaped Nova Scotia’s history and continues to impact the lives and experiences of African Nova Scotians to this day. This public report is issued by the Council of Parties of the Nova Scotia Home for Colored Children Restorative Inquiry (RI). It is one of many public reporting opportunities that have been part of the work of the RI during its mandate. The Council of Parties is the collaborative commission that leads the Restorative Inquiry, appointed as “commissioners” under the Public Inquiries Act. The council is mandated to include representation from the groups most affected by and involved in the work of the Restorative Inquiry, including former residents, the Home for Colored Children, the African Nova Scotian community, and government

Radiocarbon and geologic evidence reveal Ilopango volcano as source of the colossal ‘mystery’ eruption of 539/40 CE

Highlights • Major eruption of Ilopango volcano, El Salvador occurred in the first half of the 6th century. • Ilopango eruption is consistent with ‘mystery’ eruption of 540 CE that caused global cooling. • Magnitude 7 event ranks as one of the 10 largest on Earth in past 7000 years. • Impacts on the Maya of Central America were severe, including estimated 100,000 + fatalities. Abstract Ilopango volcano (El Salvador) erupted violently during the Maya Classic Period (250–900 CE) in a densely-populated and intensively-cultivated region of the southern Maya realm, causing regional abandonment of an area covering more than 20,000 km2. However, neither the regional nor global impacts of the Tierra Blanca Joven (TBJ) eruption in Mesoamerica have been well appraised due to limitations in available volcanological, chronological, and archaeological observations. Here we present new evidence of the age, magnitude and sulfur release of the TBJ eruption, establishing it as one of the two hitherto unidentified volcanic triggers of a period of stratospheric aerosol loading that profoundly impacted Northern Hemisphere climate and society between circa 536 and 550 CE. Our chronology is derived from 100 new radiocarbon measurements performed on three subfossil tree trunks enveloped in proximal TBJ pyroclastic deposits. We also reassess the eruption magnitude using terrestrial (El Salvador, Guatemala, Honduras) and near-shore marine TBJ tephra deposit thickness measurements. Together, our new constraints on the age, eruption size (43.6 km3 Dense Rock Equivalent of magma, magnitude = 7.0) and sulfur yield (∼9–90 Tg), along with Ilopango's latitude (13.7° N), squarely frame the TBJ as the major climate-forcing eruption of 539 or 540 CE identified in bipolar ice cores and sourced to the tropics. In addition to deepening appreciation of the TBJ eruption's impacts in Mesoamerica, linking it to the major Northern Hemisphere climatic downturn of the mid-6th century CE offers another piece in the puzzle of understanding Eurasian history of the period

Robust, reversible gene knockdown using a single lentiviral short hairpin RNA vector

Manipulation of gene expression is an invaluable tool to study gene function in vitro and in vivo. The application of small inhibitory RNAs to knock down gene expression provides a relatively simple, elegant, but transient approach to study gene function in many cell types as well as in whole animals. Short hairpin structures (shRNAs) are a logical advance as they can be expressed continuously and are hence suitable for stable gene knockdown. Drug-inducible systems have now been developed; however, application of the technology has been hampered by persistent problems with low or transient expression, leakiness or poor inducibility of the short hairpin, and lack of reversibility. We have developed a robust, versatile, single lentiviral vector tool that delivers tightly regulated, fully reversible, doxycycline-responsive knockdown of target genes (FOXP3 and MYB), using single short hairpin RNAs. To demonstrate the capabilities of the vector we targeted FOXP3 because it plays a critical role in the development and function of regulatory T cells. We also targeted MYB because of its essential role in hematopoiesis and implication in breast cancer progression. The versatility of this vector is hence demonstrated by knockdown of distinct genes in two biologically separate systems.Cheryl Y. Brown, Timothy Sadlon, Tessa Gargett, Elizabeth Melville, Rui Zhang, Yvette Drabsch, Michael Ling, Craig A. Strathdee, Thomas J. Gonda, and Simon C. Barr

Troglitazone suppresses telomerase activity independently of PPARγ in estrogen-receptor negative breast cancer cells

<p>Abstract</p> <p>Background</p> <p>Breast cancer is one the highest causes of female cancer death worldwide. Many standard chemotherapeutic agents currently used to treat breast cancer are relatively non-specific and act on all rapidly dividing cells. In recent years, more specific targeted therapies have been introduced. It is known that telomerase is active in over 90% of breast cancer tumors but inactive in adjacent normal tissues. The prevalence of active telomerase in breast cancer patients makes telomerase an attractive therapeutic target. Recent evidence suggests that telomerase activity can be suppressed by peroxisome proliferator activated receptor gamma (PPARγ). However, its effect on telomerase regulation in breast cancer has not been investigated.</p> <p>Methods</p> <p>In this study, we investigated the effect of the PPARγ ligand, troglitazone, on telomerase activity in the MDA-MB-231 breast cancer cell line. Real time RT-PCR and telomerase activity assays were used to evaluate the effect of troglitazone. MDA-MB-231 cells had PPARγ expression silenced using shRNA interference.</p> <p>Results</p> <p>We demonstrated that troglitazone reduced the mRNA expression of hTERT and telomerase activity in the MDA-MB-231 breast cancer cell line. Troglitazone reduced telomerase activity even in the absence of PPARγ. In agreement with this result, we found no correlation between PPARγ and hTERT mRNA transcript levels in breast cancer patients. Statistical significance was determined using Pearson correlation and the paired Student's <it>t </it>test.</p> <p>Conclusions</p> <p>To our knowledge, this is the first time that the effect of troglitazone on telomerase activity in breast cancer cells has been investigated. Our data suggest that troglitazone may be used as an anti-telomerase agent; however, the mechanism underlying this inhibitory effect remains to be determined.</p

Control of Stochastic Gene Expression by Host Factors at the HIV Promoter

The HIV promoter within the viral long terminal repeat (LTR) orchestrates many aspects of the viral life cycle, from the dynamics of viral gene expression and replication to the establishment of a latent state. In particular, after viral integration into the host genome, stochastic fluctuations in viral gene expression amplified by the Tat positive feedback loop can contribute to the formation of either a productive, transactivated state or an inactive state. In a significant fraction of cells harboring an integrated copy of the HIV-1 model provirus (LTR-GFP-IRES-Tat), this bimodal gene expression profile is dynamic, as cells spontaneously and continuously flip between active (Bright) and inactive (Off) expression modes. Furthermore, these switching dynamics may contribute to the establishment and maintenance of proviral latency, because after viral integration long delays in gene expression can occur before viral transactivation. The HIV-1 promoter contains cis-acting Sp1 and NF-κB elements that regulate gene expression via the recruitment of both activating and repressing complexes. We hypothesized that interplay in the recruitment of such positive and negative factors could modulate the stability of the Bright and Off modes and thereby alter the sensitivity of viral gene expression to stochastic fluctuations in the Tat feedback loop. Using model lentivirus variants with mutations introduced in the Sp1 and NF-κB elements, we employed flow cytometry, mRNA quantification, pharmacological perturbations, and chromatin immunoprecipitation to reveal significant functional differences in contributions of each site to viral gene regulation. Specifically, the Sp1 sites apparently stabilize both the Bright and the Off states, such that their mutation promotes noisy gene expression and reduction in the regulation of histone acetylation and deacetylation. Furthermore, the NF-κB sites exhibit distinct properties, with κB site I serving a stronger activating role than κB site II. Moreover, Sp1 site III plays a particularly important role in the recruitment of both p300 and RelA to the promoter. Finally, analysis of 362 clonal cell populations infected with the viral variants revealed that mutations in any of the Sp1 sites yield a 6-fold higher frequency of clonal bifurcation compared to that of the wild-type promoter. Thus, each Sp1 and NF-κB site differentially contributes to the regulation of viral gene expression, and Sp1 sites functionally “dampen” transcriptional noise and thereby modulate the frequency and maintenance of this model of viral latency. These results may have biomedical implications for the treatment of HIV latency

Onchocerciasis transmission in Ghana: Persistence under different control strategies and the role of the simuliid vectors

Background: The World Health Organization (WHO) aims at eliminating onchocerciasis by 2020 in selected African countries. Current control focuses on community-directed treatment with ivermectin (CDTI). In Ghana, persistent transmission has been reported despite long-term control. We present spatial and temporal patterns of onchocerciasis transmission in relation to ivermectin treatment history. Methodology/Principal Findings: Host-seeking and ovipositing blackflies were collected from seven villages in four regions of Ghana with 3–24 years of CDTI at the time of sampling. A total of 16,443 flies was analysed for infection; 5,812 (35.3%) were dissected for parity (26.9% parous). Heads and thoraces of 12,196 flies were dissected for Onchocerca spp. and DNA from 11,122 abdomens was amplified using Onchocerca primers. A total of 463 larvae (0.03 larvae/fly) from 97 (0.6%) infected and 62 (0.4%) infective flies was recorded; 258 abdomens (2.3%) were positive for Onchocerca DNA. Infections (all were O. volvulus) were more likely to be detected in ovipositing flies. Transmission occurred, mostly in the wet season, at Gyankobaa and Bosomase, with transmission potentials of, respectively, 86 and 422 L3/person/month after 3 and 6 years of CDTI. The numbers of L3/1,000 parous flies at these villages were over 100times the WHO threshold of one L3/1,000 for transmission control. Vector species influenced transmission parameters. At Asubende, the number of L3/1,000 ovipositing flies (1.4, 95% CI = 0–4) also just exceeded the threshold despite extensive vector control and 24 years of ivermectin distribution, but there were no infective larvae in host-seeking flies. Conclusions/Significance: Despite repeated ivermectin treatment, evidence of O. volvulus transmission was documented in all seven villages and above the WHO threshold in two. Vector species influences transmission through biting and parous rates and vector competence, and should be included in transmission models. Oviposition traps could augment vector collector methods for monitoring and surveillance